Antimicrobial peptides (AMPs) have been employed against bacterial infection in the innate defense systems of plants, insects, and animals. AMPs can target and disturb cell membrane, and hence cause the death of bacteria. The membrane lytic mechanism of AMPs makes them potential therapeutics for overcoming the antibiotic resistance.
Lipopolysaccharide (LPS, an endotoxin) is the major outer surface membrane components of gram-negative bacteria. A huge amount of LPS will be released into blood to stimulate immune response and cause sepsis when bacteria death. Human is extremely sensitive to LPS, which can cause a rise in body temperature even a very small amount of LPS (1-5 ng/kg body weight). The fever will be reduced after about 4 hours. If a patient is naturally infected with gram-negative bacteria, the fever will continue until the pathogens are completely killed because the bacteria continue to growth and release LPS. LPS can interact with macrophages to produce cytokines, such as IL-1, IL-6, and TFN-α. These cytokines signal the hypothalamus to increase the thermal set point and cause fever.
If the antibiotic for treating the bacterial infection does not have anti-endotoxin activity, it results in shock in the patients. Therefore, it is a challenge to kill bacteria and inhibit/neutralize endotoxin simultaneously to suppress overstimulation of the immune response. An anti-endotoxin agent for neutralizing LPS and suppress immune response is required.
It is therefore attempted by the applicant to deal with the above situation encountered in the prior art.